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PolymericNanoparticle-Encapsulated Hedgehog PathwayInhibitor HPI-1(NanoHHI) InhibitsSystemic Metastasesin an OrthotopicModel of HumanHepatocellular… Yang XuVenugopal ChennaChaoxin Hu2011 год

Polymeric Nanoparticle-Encapsulated Hedgehog Pathway Inhibitor HPI-1 (NanoHHI) Inhibits Systemic Metastases in an Orthotopic Model of Human Hepatocellular Carcinoma
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Аннотация: Abstract Purpose: To illustrate the prognostic significance of hedgehog (Hh) signaling in patients with hepatocellular carcinoma (HCC) and to evaluate the efficacy of a novel nanoparticle-encapsulated inhibitor of the Hh transcription factor, Gli1 (NanoHHI) using in vitro and in vivo models of human HCCs. Experimental Design: Patched1 (Ptch1) expression was detected in tumor tissue microarrays of 396 patients with HCC who underwent curative surgical resection during February 2000 to December 2002. Prognostic significance was assessed using Kaplan–Meier survival estimates and log-rank tests. The effects of NanoHHI alone and in combination with sorafenib were investigated on HCC cell lines. Primary HCC tumor growth and metastasis were examined in vivo using subcutaneous and orthotopic HCC xenografts in nude mice. Results: Elevated expression of Ptch1 in HCC tissues was significantly related to disease recurrence, as well as a shorter time to recurrence in patients with HCC. In vitro, NanoHHI significantly inhibited the proliferation and invasion of HCC cell lines. NanoHHI potently suppressed in vivo tumor growth of HCC xenografts in both subcutaneous and orthotopic milieus, and in contrast to sorafenib, resulted in significant attenuation of systemic metastases in the orthotopic setting. Furthermore, NanoHHI significantly decreased the population of CD133-expressing HCC cells, which have been implicated in tumor initiation and metastases. Conclusion: Downstream Hh signaling has prognostic significance in patients with HCC as it predicts early recurrence. Gli inhibition through NanoHHI has profound tumor growth inhibition and antimetastatic effects in HCC models, which may provide a new strategy in the treatment of patients with HCC and prevention post-operative recurrence. Clin Cancer Res; 18(5); 1291–302. ©2011 AACR.
Год издания: 2011
Авторы: Yang Xu, Venugopal Chenna, Chaoxin Hu, Hai-Xiang Sun, Mehtab Khan, Haibo Bai, Xin–Rong Yang, Qingfeng Zhu, Yun‐Fan Sun, Anirban Maitra, Jia Fan, Robert A. Anders
Издательство: American Association for Cancer Research
Источник: Clinical Cancer Research
Ключевые слова: Hedgehog Signaling Pathway Studies, Epigenetics and DNA Methylation, Cancer-related Molecular Pathways
Другие ссылки: Clinical Cancer Research (HTML)
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